Bleomycin is a glycopeptide antibiotic with strong antineoplastic activity, yet without causing immunosuppression, and thus has come into increasing use in combination chemotherapy. We propose to study the structure, conformation and mechanism of bleomycin and modified bleomycins in part through high frequency 1H NMR and natural abundance 13C NMR spectroscopy. The investigations will include the complexes of bleomycin with the following divalent metal ions: zinc, cobalt(II), cadmium and iron(II). The interaction of bleomycin with synthetic oligo-DNA will be studied with emphasis on determining the nature of the association, the sequence specificity, the nature of the cleavage product of bleomycin-directed strand scission and whether bleomycin acts catalytically. This work is designed to provide the information necessary to promote rational modifications of bleomycin in order to improve either its anticancer activity or lower its toxicity.